Description of pain associated with persistent postoperative pain after total knee arthroplasty

After total knee arthroplasty (TKA), approximately 20% of patients experience persistent postoperative pain (PPP). Although preoperative and postoperative pain intensity is a relevant factor, more detailed description of pain is needed to determine specific intervention strategies for clinical conditions. This study aimed to clarify the associations between preoperative and postoperative descriptions of pain and PPP. Fifty-two TKA patients were evaluated for pain intensity and description of pain preoperatively and 2 weeks postoperatively, and the intensities were compared. In addition, the relationship between pain intensity and PPP at 3 and 6 months after surgery was analyzed using a Bayesian approach. Descriptions of arthritis (“Throbbing” and “aching”) improved from preoperative to 2 weeks postoperative. Several preoperative (“Shooting”, “Aching”, “Caused by touch”, “Numbness”) and postoperative (“Cramping pain”) descriptors were associated with pain intensity at 3 months postoperatively, but only “cramping pain” at 2 weeks postoperatively was associated with the presence of PPP at 3 and 6 months postoperatively. In conclusion, it is important to carefully listen to the patient’s complaints and determine the appropriate intervention strategy for the clinical condition during perioperative pain management.

The association between the preoperative/postoperative 2-week description of pain and the presence or absence of persistent pain at 3 and 6 months postoperatively was analyzed with a Bernoulli distribution.As the GLMM did not converge with the MCMC, the Generalized Linear Model (GLM) was used to exclude random effects (Table 4).As a result, only cramping pain at 2 weeks postoperatively was associated with the presence of persistent pain at 3 months (estimate: 1.42, 95% CI 0.60-2.37)and 6 months (estimate: 0.95, 95% CI 0.21-1.78)postoperatively.None of the preoperative descriptions showed any significant associations.

Discussion
In this study, we focused on the description of pain, investigated changes before and after TKA, and examined their relationship with persistent pain at 3 and 6 months postoperatively.The main findings showed the following: (1) descriptions of pain, such as "throbbing, " "sharp, " "aching, " and "tiring/exhausting, " improved with TKA, while "tender" and "itching" worsened slightly; (2) some preoperative descriptions ("shooting, " "aching, " "caused by touch, " and "numbness") and one postoperative description ("cramping pain") were associated with NRS at 3 months; and (3) only postoperative "cramping pain" was associated with the presence of persistent pain at 3 and 6 months.The median preoperative descriptions "throbbing" and "aching" were moderate to severe 20 , but improved significantly postoperatively."Throbbing" and "aching" pains are caused by joint arthritis, suggesting that the joint problem has been improved by TKA [21][22][23] .Since pain is also associated with fatigue 24 , it is considered that those with "tiring/exhausting" pain descriptions showed improvements in pain intensity.On the other hand, those with pain descriptions of "tender" and "itching" showed slight worsening.Two weeks after surgery, when the wound healed and the staples was removed, the residual peripheral/central sensitization caused by the surgical invasion Table 3. GLMM for the association between NRS at 3 months and descriptions of pain.* When the 95% CI did not cross zero, it was considered significant., and these temporarily worsening pain symptoms improve over time.In the SFMPQ-2 subscale, only neuropathic pain alone showed no improvement.As arthroplasty does not improve nerve problems, patients with preoperative neuropathic pain should be considered for perioperative treatment, which includes pharmacotherapy 18 and electrical stimulation 25,26 .
The GLMM analysis of Poisson distribution (description of pain model) with individual ID as a random effect and 22 descriptions as fixed effects showed that several preoperative ("shooting pain, " "aching pain," "caused by touch, " and "numbness") and postoperative ("cramping pain") descriptions were associated with the NRS at 3 months.However, the GLM analysis of the Bernoulli distribution showed that only postoperative "cramping pain" was associated with the presence of PPP at 3 and 6 months postoperatively.
The pain expression "cramping pain" is described when the muscles are over-contracted.This type of pain is typically caused by fatigue associated with overuse 27 .Muscle weakness after TKA has been attributed not only to peripheral skeletal muscles, but also to central nervous system control, including the spinal cord and cerebral cortex 28,29 .This may also contribute to the occurrence of cramping pain.Pain expressions reflecting motor control problems have also been observed in patients with phantom limb pain 17 , intractable pain after nerve injury 16 , and central post-stroke pain 30 .Some studies have reported that these patients show improvements with interventions for the sensory-motor system using mirror therapy and virtual reality environments 16,17,30 .In addition, interventions that consider the central nervous system for perioperative TKA/KOA, such as repetitive transcranial magnetic stimulation 31 , transcranial direct current stimulation 32 , neuromuscular electrical stimulations 33 , motor imagery 34 , have been reported to be effective.Therefore, it is necessary to verify whether such specific interventions that take into account central nervous system control can improve cramping pain and prevent persistent pain in the management after TKA.
This study had several limitations.First, psychological factors [6][7][8]35 , central sensitization 36 , and neuropathic pain 7 associated with PPP were not evaluated in detail. Inaddition, characteristics of the participants, pain duration, blood loss, TKA type associate with absent or present PPP at 6 months postoperatively in this study.These factors are probably reflected in the individual ID that was found to be associated with pain intensity at 3 months postoperatively in the GLMM. Secod, the description of pain at 3 and 6 months postoperatively was not measured.It remains to be clarified whether the same description of pain as at 2 weeks postoperatively was continued to be used.Future studies could analyze these associations by assessing catastrophic thinking [37][38][39] , anxiety and depression 40 , central sensitization-related symptoms 36,39,41,42 , and neuropathic pain 7 , as well as by examining pain descriptions at 3 and 6 months.Third, central/peripheral neuromuscular activity measurements, such as functional magnetic resonance imaging, motor-evoked potentials, and electromyography, were not performed.Future studies should include these techniques while considering the underlying neuromuscular activity.
This study focused on the description of pain and clarifying its association with PPP after TKA.We conclude that, in perioperative pain management, it is important to carefully listen to the patient's complaints and determine the appropriate intervention strategy for the clinical condition.

Participants
The participants were hospitalized patients who underwent primary unilateral or bilateral TKA at Kyowakai Hospital between April 2018 and December 2023.Participants received standardized anesthesia, surgery, postoperative pain management, and guideline-based physical therapy 43,44 .The exclusion criteria were dementia, higher brain dysfunction, inability to respond to the questionnaire adequately, and revision TKA.The study was approved by the Kyowakai Hospital Ethical Review Committee (approval number: Kyorin18-1), and all participants provided written informed consent in accordance with the Declaration of Helsinki.

Measures
Participant characteristics (age, sex, body mass index [BMI], preoperative pain duration, unilateral or bilateral surgery, Kellgren-Lawrence [KL] grade, operative time, blood loss, wound size, and TKA type) were collected from patient charts.A few days before and two weeks after surgery when the wound is healed and the staples are removed, the NRS was used to assess pain intensity, and the SFMPQ-2 was used to description of pain.In addition, the NRS was obtained 3 and 6 months postoperatively via mail or telephone.The preoperative and 2-weeks postoperative NRS and SFMPQ-2 were assessed in all participant, but lack of contact resulted in one missing NRS score at postoperative 3 or 6 months.
The NRS is the most commonly used measure of pain intensity with an 11-point scale ranging from 0 (no pain) to 10 (worst imaginable pain).The minimal clinically important difference is 22% for acute pain 45 and 33% for chronic pain 46 .In this study, persistent pain was defined as moderate or severe pain (NRS≥3) persisting at 3 or 6 months postoperatively 20,47,48 .
The SFMPQ-2 is used to assess the intensity and description of pain.It consists of 22 sensory expressions of pain, with each item rated on an NRS scale of 0-10.The higher the intensity of pain, the higher the total score.The SFMPQ-2 has four subclasses (continuous pain, intermittent pain, affective pain, and neuropathic pain) 49 .

Statistical analysis
Characteristics of participants were compared using the Mann-Whitney U test for continuous variables and Chi-square test or Fisher's exact test was used for categorical variables.
The NRS assessed the preoperative and 2 weeks/3 months/6 months postoperative scores and compared them using the Friedman test (post hoc Bonferroni correction).In addition, each item was compared using the Wilcoxon signed-rank test preoperatively and 2 weeks postoperatively.The association between SFMPQ-2 results preoperatively and 2 weeks postoperatively and pain intensity at 3 and 6 months postoperatively was analyzed by GLMM with individual ID as a random effect.A Bayesian estimation of the posterior distribution was performed using the MCMC algorithm 50 .MCMC is a method for obtaining an approximate solution to the integral through Monte Carlo integration using random numbers generated by a Markov chain, which enables a reasonable estimation for small sample sizes and missing values.The Z-score for each item was used in the analysis.An uninformative prior distribution was used, the number of iterations was set to 2000, burn-in period to 1000, number of chains to four, and 95% CI were given.Rhat values were used to evaluate MCMC convergence, wherein a Rhat value of <1.1 suggested good convergence.

Table 1 .
Characteristics of the participants.Mean±standard deviation † assessed by Mann-Whitney U test or Chi-squared test or Fisher's Exact Test.PPP, persistent postoperative pain; BMI, body mass index; Uni, unilateral; Bil, bilateral; KL grade; Kellgren-Lawrence grade.

Table 2 .
Comparison of the preoperative/postoperative description of pain.

Table 4 .
GLM for the association between persistent postoperative pain and descriptions of pain.* When the 95% CI did not cross zero, it was considered significant.GLM, Generalized Linear Model; PPP, persistent postoperative pain; CI, confidence interval.